JPH0120245B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to cellulose derivative hollow fibers, and more particularly to permselective hollow fibers which have high water permeability, high albumin protein rejection, and extremely low clogging.

In recent years, the need for separation of substances, especially separation based on large and small molecular weight, has been rapidly increasing in a wide range of fields such as seawater desalination, wastewater treatment, artificial kidneys, and the food industry. Attention has been paid. In particular, hollow membranes have the advantage that the membrane area per unit volume can be increased and space efficiency can be increased, and that they do not require a support and have high pressure resistance compared to flat membranes.

In particular, membranes with high water permeation rates and sharp fractionation characteristics have high utility value in filtration concentration in the food industry, production of sterile water, and blood purification through blood filtration. As such hollow fibers, those molded from cellulose, cellulose ester, polyacrylonitrile, polymethyl methacrylate, polyvinyl chloride, ethylene-vinyl alcohol supply material, etc. are known. Currently, polyacrylonitrile-based hollow fibers, cellulose derivative hollow fibers, and the like have been proposed as permselective hollow fibers that have a high water permeation rate and a high protein rejection rate.

Although the former polyacrylonitrile hollow fiber has a high water permeation rate for pure water, the water permeation rate for protein aqueous solutions generally decreases significantly due to protein adsorption, and it is difficult to apply it as a material in this field. Ru. Unlike acrylonitrile-based membranes, the latter cellulose derivative hollow fibers are excellent materials because they hardly adsorb proteins, but they cannot block proteins at a high rate and have a sufficiently high water permeation rate. Even when the filtration rate was increased, when an aqueous protein solution was filtrated, the pores of the membrane were blocked by the protein, and the filtration rate was usually significantly reduced.

For example, according to the cellulose ester hollow fiber disclosed in JP-A-54-6916, the water permeation rate of pure water is 120 to 180 ml/hr.m ² . mmHg, which is relatively high, whereas that of albumin aqueous solution is 40-52ml/hr.m ² .
mmHg, and the reduction rate ranges from 60 to 70%.

That is, at present, a cellulose derivative hollow fibrous membrane that has a high water permeation rate, a high protein rejection rate, and is resistant to clogging has not yet appeared, and its development has been awaited.

An object of the present invention is to provide a cellulose derivative hollow fiber that satisfies the above-mentioned properties, namely, high water permeability, high protein inhibition, and resistance to clogging. Its gist is that it is a hollow fiber obtained by wet-spinning or dry-wet-spinning a mixture of two or more cellulose derivatives with different properties, and the water permeation rate A of an aqueous serum albumin solution is 150 to 500 ml/hr.m ² . mmHg, and the ratio of that to the water permeation rate B of pure water, that is, A/B
The ratio is 0.6 or more and the serum albumin inhibition rate is
It is a permselective hollow fiber characterized by a permselectivity of 90% or more.

Here, the serum albumin aqueous solution is 0.2g/100c.c.
The inhibition rate is calculated using the following formula.

Rejection rate (%) = (undiluted serum albumin concentration - liquid serum albumin concentration) / undiluted albumin concentration x 100 The cellulose derivative hollow fiber of the present invention has a water permeation rate of an aqueous serum albumin solution of 150 to 500 ml/hr.m ² .
It is necessary to be in the range of mmHg, and if it is less than 150, the water permeation rate is insufficient and the membrane area must be increased, resulting in a large filtration device, which is industrially disadvantageous. Moreover, when it exceeds 500, the inhibition rate of serum albumin decreases drastically, making it difficult to use in the field where protein is to be inhibited at a high rate.

The value of the ratio A/B between the water permeation rate A and the pure water rate B of the serum albumin aqueous solution is an extremely important point in the present invention. In other words, the value of A/B is at least
0.6 is an essential requirement. If A/B is less than 0.6, clogging is severe and stable flow operation cannot be performed for a long time.

Furthermore, as an essential requirement of the present invention, the albumin inhibition rate to the serum albumin aqueous solution must be 90% or more. If it is less than 90%, problems such as a decrease in the recovery rate during protein recovery and protein leakage during blood filtration may occur, which is undesirable.

As mentioned above, polyacrylonitrile membranes are currently used as membranes for protein separation, but this membrane easily adsorbs proteins and is easily clogged, so although it has a high protein rejection rate, it has a high A/B When the ratio is between 0.2 and 0.4, the filtration efficiency decreases significantly. On the other hand, although the hollow fiber disclosed in JP-A-54-6916 has an albumin rejection rate of 90% or more, the A/B value is 0.3 to 0.58, which is the same as that of polyacrylonitrile membranes, and clogging is large in both cases. . In other words, the present invention has achieved a dramatic improvement in the performance of hollow fibers, which was unimaginable with conventional membranes.

In order to produce the hollow fibers of the present invention, it is preferable to form the hollow fibers by a wet or wet-dry method from a stock solution consisting of a mixture of two or more cellulose derivatives with different properties and a combination of a non-volatile organic solvent. As a result, hollow fibers with a sufficiently large value of permeation rate ratio A/B, which is a measure of membrane clogging, can be obtained which is resistant to clogging.

The cellulose derivatives used in the present invention are as follows (a) to
It is a mixture of cellulose derivatives consisting of any combination of (d).

(a) Combination of cellulose acetates with different degrees of acetylation.

(b) A combination of cellulose acetate and cellulose propionate.

(c) Combination of cellulose acetate and ethyl cellulose.

(d) A combination of cellulose derivatives that differ only in degree of polymerization, with a difference in [η] of at least 0.1.

Among these combinations, cellulose acetate having different degrees of acetylation is particularly preferred as a combination of cellulose derivative mixtures that provides good raw material availability, good spinnability, and good membrane performance. In other words, cellulose diacetate with a degree of acetylation of 50 to 57% (hereinafter
A preferred combination of CDA) and cellulose triacetate (hereinafter referred to as CTA) with an acetylation degree of 58 to 62% is preferable.The composition of CDA and CTA is CDA/CTA=
The ratio is preferably 10/1 to 1/2, and the effect becomes significantly higher when the proportion in the stock solution is 15 to 20 wt%.

Next, the solvent used for producing the hollow fibers of the present invention is preferably a nonvolatile organic solvent, that is, an organic solvent having a boiling point of 100° C. or higher. Examples include dimethyl sulfoxide, dimethylacetamide, dimethylformamide, acetic acid, and trimethyl phosphate. When forming hollow fibers using such a stock solution, wet spinning in an aqueous coagulation bath, or dry-wet spinning, in which the fiber is coagulated after running in air or an inert gas, is employed.

Furthermore, when forming hollow fibers by this method, it is necessary to inject a liquid into the hollow part in order to maintain the hollow part, and it is appropriate to use a double tube type spinneret. Any liquid may be used as the liquid to be injected into the interior, but liquids having the same composition as the coagulation bath, hydrocarbons, fatty acid esters, etc. are preferably used.

In this way, it is possible to make hollow fibers by coagulating the stock solution from the spinneret and the hollow stock solution injected with liquid from inside in an aqueous coagulation bath, but it is necessary to further increase the strength of the hollow fibers and improve processability and handleability. It is also possible to stretch in warm water at 20 to 90°C depending on the situation.

The hollow fibers thus obtained may be used as they are, or may be plasticized with glycerin and dried if necessary.

The cellulose derivative hollow fibers obtained in this manner have a high water permeation rate, a high rejection rate against proteins, and are resistant to membrane clogging. Therefore, the hollow fiber of the present invention is effective for concentrating plasma proteins and various enzyme proteins, and can be used in fields such as the medical field, the pharmaceutical industry, and the food industry.

Further, the present invention will be explained in detail with reference to Examples.

Example 1 9 parts of cellulose diacetate with a degree of acetylation of 55% and 9 parts of cellulose triacetate with a degree of acetylation of 60% were dissolved in dimethylacetamide and defoamed by filtration to obtain a spinning stock solution. The spinning stock solution was poured into the outer annular part of the double-tube structure spinneret at a rate of 3.2 cc/min, and the 60% dimethylacetamide aqueous solution was added into the inner pipe part at a rate of 2.1 cc/min.
It was extruded at a rate of cc/min. The spinneret has an outer annular portion with a diameter of 4 mmφ, an inner tube with an outer diameter of 2 mmφ, and an inner diameter of 1 mmφ.
It was hot. The stock solution containing the core material extruded from the nozzle is passed through air for 10 cm and introduced into a 30% dimethylacetamide aqueous solution kept at 20°C to solidify30.
Taken off at a speed of m/min, then placed in hot water at 70°C.
It was stretched 1.2 times and rolled up at a speed of 36 m/min.

The obtained hollow fibers were thoroughly washed with water, immersed in a 30% glycerin aqueous solution for 10 minutes, and then dried at 50°C. The obtained hollow fiber had an inner diameter of 265 μm and a wall thickness of 40 μm.
After making a mini module by bundling 100 of these hollow fibers, pour pure water from the outside of the hollow fibers at 0.2g/100.
cc of serum albumin aqueous solution was supplied to each membrane, the membrane was pressurized so that the pressure difference on both sides was 150 mmHg, and the permeate that permeated through the hollow fiber membrane was taken out from the hollow part of the hollow fiber, and its permeation rate and albumin in the permeate were measured. The concentration was measured. As a result, the permeation rate for pure water and albumin solution is B = 250, respectively.
ml/ ^m2 . hr.mmHg A=220, and the ratio A/B is
It was 0.88. The albumin inhibition rate is 94.5%.
It had sufficiently satisfactory performance.

Example 2 6 parts of cellulose triacetate with a degree of acetylation of 59.5% was dissolved in 85 parts of dimethylformamide, and then 9 parts of cellulose diacetate with a degree of acetylation of 53.5% was added and dissolved. The spinning dope, which had been deaerated by filtration, was extruded from the annular part of the same spinneret as in Example 1 at a rate of 6.0 cc/min, while methyl oleate was extruded from the inner tube part at a rate of 4.8 cc/min. The stock solution containing the core material extruded from the nozzle was allowed to pass through 7 cm of air, and then heated to 20°C at 10°C.
% dimethylformamide aqueous solution to solidify it, take it off at a speed of 60 m/min, then stretch it 1.1 times in water at 30°C, wind it up at a speed of 66 m/min, thoroughly wash it with water, and then plasticize it with a 40% glycerin aqueous solution. Air dried.

The obtained hollow fibers had an inner diameter of 290 μm and a wall thickness of 30 μm, and 100 of these hollow fibers were bundled and both ends were bonded with resin to create a mini module.

In the same manner as in Example 1, the permeation rates B and A of pure water and serum albumin aqueous solution were measured and found to be 400 ml/hr.m ² . At mmHg520, A/B=0.77 and the serum albumin inhibition rate was 92.5%.

Example 3 7 parts by weight of cellulose acetate with a degree of acetylation of 55% and 7 parts by weight of cellulose acetate with a degree of acetylation of 61.5% were mixed, 86 parts by weight of dimethylacetamide was added, and the mixture was heated and dissolved at 120°C for 3 hours to undergo desorption. A spinning dope was prepared by foaming. The spinning stock solution was poured at 2.0 cc/min from the outer annular part of the spinneret with a double-tube structure, while the 20% dimethylacetamide aqueous solution was poured at 0.8 cc/min from the inner pipe part.
Extrude at a rate of min and solidify immediately 6m/min
I rolled it up at speed. The spinneret was placed in a 40% dimethylacetamide aqueous solution at 30° C., and the size of the spinneret was an outer annular portion with a diameter of 1 mm, an inner tube with a diameter of 0.8 mm, and an inner diameter of 0.5 mm.

The obtained hollow fibers were thoroughly washed with water, sufficiently plasticized with a 40% aqueous glycerin solution, and then dried at 70°C. The inner diameter of the hollow fiber is 450μ and the wall thickness is 45μ.
I created a bundle of 200 pieces and a mini module. Pure water and a 0.2 g/100 c.c. serum albumin aqueous solution were supplied under pressure to the inside of the hollow fiber, and the liquid that permeated through the hollow fiber membrane was collected from the outer wall and its water permeation rate was measured. The permeation rates of pure water and albumin aqueous solution are each B=670ml/m ² . hr.mmHg, A=480, the ratio is 0.72, and the serum albumin inhibition rate is
It showed a good performance of 91.8%.

Example 4 8 parts of ethyl cellulose with a degree of etherification of 2.5 and 8 parts of cellulose diacetate with a degree of acetylation of 55% were dissolved in 84 parts of dimethyl sulfoxide and subjected to extensive defoaming to obtain a spinning dope. Using the same spinneret as in Example 1, the spinning dope was extruded from the inner tube at a rate of 5 c.c./min and ethylene glycol was extruded at a rate of 3.0 cc/min, passed through air for 5 cm, and heated to 40% at 20°C. Pour into dimethyl sulfoxide aqueous solution and solidify 40
It was rolled up at a speed of m/min. Afterwards, wash thoroughly with water.
Plasticized in 50% glycerin aqueous solution 70
Dry at °C. The obtained hollow fiber had an inner diameter of 295 μm,
The wall thickness was 41 μm, and the water permeation rate of pure water and albumin aqueous solution after modularization was measured in the same manner as in Example 1. The water permeation rate A of the albumin aqueous solution is 350ml/hr.
^m2 ． The water permeation rate B of pure water at mHg is 470ml/hr.m ² .
The A/B value in mmHg was 0.74 and the albumin inhibition rate was 94.0%.

Claims (1)

[Scope of Claims] 1. A hollow fiber obtained by wet-spinning or dry-wet-spinning a mixture of cellulose derivatives consisting of a combination of any of the following (a) to (d), which has a water permeability rate of an aqueous serum albumin solution. A is 150-500ml/hr.
m ² ·mmHg, the ratio to the water permeation rate B of pure water, that is, the value of A/B, is 0.6 or more, and the rejection rate of the albumin is 90% or more. (a) Combination of cellulose acetates with different degrees of acetylation. (b) A combination of cellulose acetate and cellulose propionate. (c) Combination of cellulose acetate and ethyl cellulose. (d) A combination of cellulose derivatives that differ only in degree of polymerization, with a difference in [η] of at least 0.1. 2 The mixture of cellulose derivatives has an acetylation degree of 50-57%
The permselective hollow fiber according to claim 1, which is a mixture consisting of a combination of cellulose diacetate with a degree of acetylation of 58 to 62% and cellulose triacetate with an acetylation degree of 58 to 62%.